Unlocking the Secrets of Hemophilia

Since the twentieth century, scientific discoveries have significantly advanced the understanding and treatment of hemophilia. As mentioned earlier, in 1936, scientists discovered that plasma could be used to treat hemophilia. In 1937, two researchers at Harvard Medical School, A. J. Patek and F.H.L. Taylor, discovered an improved way to treat the disease. They discovered that solids removed from plasma, rather than whole plasma, could be injected to make blood clot faster. In 1939, Kenneth Brinkhous at the University of North Carolina demonstrated that people with hemophilia lack a component of the plasma, which he called antihemophilic factor. Today, this substance is known as factor VIII.

In 1944, a doctor in Buenos Aires, Argentina, named Alfredo Pavlovsky found in laboratory tests that blood from one patient with hemophilia could cause the blood of another hemophilia patient to clot. This meant that there were two different clotting factors in the blood (later identified as factors VIII and IX). A patient could lack one but have the other. The same year, an American biochemist at Harvard Medical School, Edwin Cohn, developed a technique for separating plasma into its component parts. This process, called fractionation, allowed Cohn and his colleagues to demonstrate that one of the blood fractions, named Cohn Fraction I, contained the blood-clotting factors. Armand Quick, an American doctor, reached the same conclusion that year. The work of these researchers laid the foundation for advances in understanding hemophilia for decades to come.

Advances in Treating Hemophilia

In 1955, three American pathologists, Kenneth Brinkhous, Robert Langdell, and Robert Wagner, developed the first method of giving patients infusions of factor VIII. Unfortunately, there were problems with this early form of treatment. In the 1950s, plasma from animals such as pigs and cows was used in hemophilia treatments, and many people had serious allergic reactions to these animal products.

In 1964, R. G. Macfarlane identified the process by which various factors work in series to clot blood. In this process, the factors line up like a series of dominoes—when the first one is knocked over, it affects the next, which affects the next, and so on. In the blood, this sequential activation of clotting factors is called the coagulation cascade. Scientists now better understood how blood clots were formed and began to search for new ways to treat hemophilia.

Frozen Factors

In the middle of the 1960s, Judith Pool, a doctor working at Stanford University, made a discovery that tremendously advanced hemophilia treatment. She discovered that slowly thawing frozen plasma resulted in the precipitation, or depositing, of solid material at the bottom of a container. Such deposits are called cryoprecipitates (cryo means “frozen”). Pool found that the cryoprecipitates were high in factor VIII. They had much greater power to make blood clot than whole plasma did.

Cryoprecipitates allowed the hemophilia patient to treat himself or herself from home instead of having to travel to a hospital. The cryoprecipitate could be kept frozen at home, and if necessary, a local doctor could perform the infusion after thawing some of the patient’s supply of the material. Following Pool’s initial work, researchers at the Plasma Fractionation Laboratory (PFL) in Oxford, England, produced cryoprecipitates of various other important clotting factors, such as factors VII, XI, and XIII. By 1968, freeze-drying was found to be possible with the cryoprecipitates. This resulted in a powdered form of the clotting factor that could be kept at home and used as necessary.

Dangers Lurking in the Blood Supply

However, the use of cryoprecipitates was not without drawbacks. The plasma from which the precipitates are made is the result of pooling a large quantity of plasma from thousands of individual donors. One problem with pooling blood from so many different people is that it increases the chance of contamination by a virus. Viruses present in plasma will be passed on to those who use the plasma or precipitates made from it. A few of the most serious viruses that can be passed on are hepatitis B and C, which cause inflammation of the liver, and human immunodeficiency virus (HIV), the virus responsible for acquired immunodeficiency syndrome (AIDS). From 1979 to 1985, thousands of people with hemophilia worldwide were infected with hepatitis and HIV viruses from using contaminated blood products.

Reducing Risk

In the 1980s, methods using heat and chemicals were developed that inactivated viruses such as HIV, making it safer to use plasma and plasma precipitates to treat hemophilia. These methods are still used today. Another way to reduce the risk of catching diseases from blood products is to use a man-made substance that would encourage blood to clot. For example, in 1977, Professor Pier Mannucci of the University of Milan in Italy discovered that a compound called desmopressin could be used to treat mild cases of hemophilia type A and von Willebrand disease. Desmopressin is a synthetic, or man-made, hormone, a compound that affects the way that other compounds or organs in the body behave. Desmopressin increases the release of factor VIII and von Willebrand factor, which in some cases of mild hemophilia and von Willebrand disease is enough to address the problem.